Two recent developments have made possible a comprehensive investigation of the structural basis of capillary permeability in all types of blood capillaries. One concerns the finding that glycogen and dextran molecules (or particles) injected into the blood stream can be stained in tissues by lead. The other is the introduction of mass tracers of small molecular weight (myoglobin, and hemepeptides) which can be detected in the tissues by a histochemical reaction based on their peroxidatic activity. These newly introduced tracers range in size from approximately 70 to approximately 350A, and hence qualify as probe molecules for the small (diam. approximately 90A) and large (diam. approximately 600A) pores of the capillary wall. Work under this project aims at identifying the structural equivalents of the two pore systems in muscular and visceral capillaries, and at finding the relationship of these pores to the fenestrae, plasmalemmal vesicles, and intercellular junctions of the endothelium. BIBLIOGRAPHIC REFERENCES: N. Simionescu, M. Simionescu, and G. E. Palade. Permeability of muscle capillaries to small heme-peptides. Evidence for the existence of patent transendothelial channels. J. Cell Biol. 1975, 64:586-607. M. Simionescu, N. Simionescu, and G. E. Palade. Characteristic endothelial junctions in sequential segments of the microvasculature. J. Cell Biol. 1974, 63:316a (abstr.)